Regulation of actin catch-slip bonds with a RhoA-formin module

• Type of Material: Article
• Authors: Cho-yin Lee, Georgia Institute of Technology; Jizhong Lou, Chinese Academy of Sciences; Kuo-Kuang Wen, University of Iowa; Melissa McKane, University of Iowa; Suzanne G. Eskin, Georgia Institute of Technology; Peter A. Rubenstein, University of Iowa; Shu Chien, University of California San Diego; Shoichiro Ono, Emory University; Cheng Zhu, Emory University; Larry McIntire, Emory University
• Language: English
• Date: 2016-10-12
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2016.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep35058
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 6
• Start Page: 35058
• End Page: 35058
• Grant/Funding Information: This work was supported by NIH grants (HL18672, HL70537 to L.V.M.; AI044902, HL132019to C.Z.; AR48615 to S.O.; GM33689 to P.A.R.) and Army Research Office grant W911NF-16-1-0257 to C.Z.; The computational resources were provided by National Supercomputing Center Tianjin Center under the support by the National Basic Research Program of China (2014CB910202 to J.L.).
• Keywords: ADHESION; FILAMENT ELONGATION; Biophysical chemistry; Science & Technology; MECHANISM; ORGANIZATION; Single-molecule biophysics; INDUCED NUCLEATION; HOMOLOGY-2 DOMAIN; MDIA1; CELL; TENSION; Multidisciplinary Sciences; PROTEINS
• Research Categories: Engineering, Biomedical; Biophysics, General

Abstract

The dynamic turnover of the actin cytoskeleton is regulated cooperatively by force and biochemical signaling. We previously demonstrated that actin depolymerization under force is governed by catch-slip bonds mediated by force-induced K113:E195 salt-bridges. Yet, the biochemical regulation as well as the functional significance of actin catch bonds has not been elucidated. Using AFM force-clamp experiments, we show that formin controlled by RhoA switches the actin catch-slip bonds to slip-only bonds. SMD simulations reveal that the force does not induce the K113:E195 interaction when formin binds to actin K118 and E117 residues located at the helical segment extending to K113. Actin catch-slip bonds are suppressed by single residue replacements K113E and E195K that interrupt the force-induced K113:E195 interaction; and this suppression is rescued by a K113E/E195K double mutant (E/K) restoring the interaction in the opposite orientation. These results support the biological significance of actin catch bonds, as they corroborate reported observations that RhoA and formin switch force-induced actin cytoskeleton alignment and that either K113E or E195K induces yeast cell growth defects rescued by E/K. Our study demonstrates how the mechano-regulation of actin dynamics is modulated by biochemical signaling molecules, and suggests that actin catch bonds may be important in cell functions.